Previous experiments have indicated that widespread necrotic arteritis and arterial hypertension induced in rabbits by certain experimental renal alterations (wrapping one kidney in silk saturated with turpentine and removing the other kidney seven days later) can be dissociated in other experimental situations. These findings have led to the hypothesis that induction of hypertension and necrotic arterial lesions in this experimental model are controlled by independent but possibly related mechanisms. As yet unidentified factors are probably produced in the altered (silk-wrapped) kidney and/or the adrenal glands and are moderated through or by some factor (s) from the contralateral (unoperated) kidney. We propose to elucidate and differentiate the mechanisms for the pathogenesis of the hypertension and necrotic arterial lesions in this model. Biochemical, physiologic and morphologic parameters relating to the arterial lesions, the renin-angiotensin-aldosterone axis and renomedullary substances, antihypertensive and/or vasodepressor, will be studied. Intervention in the model utilizing substances that inhibit some of the compounds of these systems, in particular inhibitors of angiotensin converting enzyme and of prostaglandin synthesis, have been undertaken. The effects of autotransplants of renal tissue, cortex and/or medulla, on the model will also be investigated. Radioimmunoassay techniques that have recently been perfected will facilitate the analytical studies.